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Clinical and Experimental Medicine Nov 2023Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2... (Meta-Analysis)
Meta-Analysis Review
Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2 mutations are rarely expressed in several cancers, when they occur, they can activate the HER2 signaling pathway. In recent years, studies have shown that anti-HER2 drugs have promising efficacy in patients with HER2 mutations. Based on keywords, we searched databases, such as PubMed, Embase, and Cochrane Library, and the main conference abstracts. We extracted data on objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) from studies on the efficacy of anti-HER2 therapies in patients with HER2-mutated cancers, and analyzed grade 3 or higher adverse events (AEs). We included 19 single-arm clinical studies and 3 randomized controlled trials (RCTs), containing a total of 1017 patients with HER2 mutations, involving seven drugs and nine cancers, and 18 studies enrolled a high proportion of heavily pretreated patients who had received multiple lines of therapy. Our results showed pooled ORR and CBR of 25.0% (range, 3.8-72.7%; 95% CI, 18-32%) and 36.0% (range, 8.3-63.0%; 95% CI, 31-42%) for anti-HER2 therapy in HER2-mutated cancers. The pooled median PFS, OS, DOR were 4.89 (95% CI, 4.16-5.62), 12.78 (95% CI, 10.24-15.32), and 8.12 (95% CI, 6.48-9.75) months, respectively. In a subgroup analysis, we analyzed the ORR for different cancers, showing 27.0, 25.0, 23.0, and 16.0% for breast, lung, cervical, and biliary tract cancers, respectively. ORR analyses were performed for different drugs as monotherapy or in combination, showing 60.0% for trastuzumab deruxtecan (T-DXd), 31.0% for pyrotinib, 26.0% for neratinib combined with trastuzumab, 25.0% for neratinib combined with fulvestrant, 19.0% for trastuzumab combined with pertuzumab, and 16.0% for neratinib. In addition, we found that diarrhoea, neutropenia, and thrombocytopenia were the most common grade ≥ 3 AEs associated with anti-HER2 therapeutic agents. In this meta-analysis of heavily pretreated patients with HER2 mutations, anti-HER2 therapies, DS-8201 and trastuzumab emtansine, showed promising efficacy and activity. Anti-HER2 therapies showed different efficacies in different or the same cancer settings and all had a tolerable safety profile.
Topics: Humans; Female; Trastuzumab; Receptor, ErbB-2; Ado-Trastuzumab Emtansine; Neoplasms; Breast Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37120775
DOI: 10.1007/s10238-023-01072-7 -
Frontiers in Oncology 2023Overexpression of heat shock proteins (HSPs) has been observed in a wide range of human tumors, and there is an increasing evidence demonstrated that HSPs play a key...
BACKGROUND
Overexpression of heat shock proteins (HSPs) has been observed in a wide range of human tumors, and there is an increasing evidence demonstrated that HSPs play a key role in tumor progression. Several studies were conducted to explore the clinicopathological characteristics and prognostic value of HSPs in hepatocellular carcinoma (HCC), but the results remain controversial. To address this gap, we conducted a systematic review and meta-analysis.
METHODS
The eligible literature was obtained from PubMed, Cochrane library, Web of science, Embase, Chinese National Knowledge Infrastructure and Wan Fang databases. We used the odds ratio (OR) and hazard ratio (HR) as the suitable parameters to assess the clinicopathological features and prognostic value of HSPs in HCC patients.
RESULTS
The meta-analysis results showed that HSPs expression was associated with overall survival (OS) of HCC patients (HR = 1.61, 95%CI = 1.22-2.13, =0.001, = 62.7%). In addition, the pooled results suggested that HSPs expression was significantly correlated with tumor differentiation (OR = 1.33, 95%CI = 1.08-1.65, = 0.907), vascular invasion (OR = 1.31, 95%CI = 1.02-1.69, = 0.921) and lymphatic metastasis (OR=1.98, 95%CI= 1.70-2.31, = 0.740). Meanwhile, the subgroup analysis showed a significant correlation between the expression of HSP27 (HR=1.69, 95%CI = 1.24-2.31, = 0.674) and HSP90α (HR=2.03, 95%CI = 1.73-2.40, = 0.743) with OS of HCC patients.
CONCLUSIONS
Our meta-analysis confirms that HSPs expression is closely associated with a worse prognosis in HCC patients, and may be directly involved in tumor differentiation and distant metastasis. In addition, the subgroup analysis results demonstrate that the expression of HSP27 and HSP90α can be served as potential prognostic predictors of HCC.
PubMed: 37601679
DOI: 10.3389/fonc.2023.1169979 -
PloS One 2024Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results.... (Meta-Analysis)
Meta-Analysis
Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results. Currently, no reliable biomarkers are available to predict the survival, recurrence, and progression of meningioma patients in clinical practice. This study aims to evaluate the prognostic value of immunohistochemistry-based (IHC) biomarkers of meningioma patients. A systematic literature search was conducted up to November 2023 on PubMed, CENTRAL, CINAHL Plus, and Scopus databases. Two authors independently reviewed the identified relevant studies, extracted data, and assessed the risk of bias of the studies included. Meta-analyses were performed with the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). The risk of bias in the included studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool. A total of 100 studies with 16,745 patients were included in this review. As the promising markers to predict OS of meningioma patients, Ki-67/MIB-1 (HR = 1.03, 95%CI 1.02 to 1.05) was identified to associate with poor prognosis of the patients. Overexpression of cyclin A (HR = 4.91, 95%CI 1.38 to 17.44), topoisomerase II α (TOP2A) (HR = 4.90, 95%CI 2.96 to 8.12), p53 (HR = 2.40, 95%CI 1.73 to 3.34), vascular endothelial growth factor (VEGF) (HR = 1.61, 95%CI 1.36 to 1.90), and Ki-67 (HR = 1.33, 95%CI 1.21 to 1.46), were identified also as unfavorable prognostic biomarkers for poor RFS of meningioma patients. Conversely, positive progesterone receptor (PR) and p21 staining were associated with longer RFS and are considered biomarkers of favorable prognosis of meningioma patients (HR = 0.60, 95% CI 0.41 to 0.88 and HR = 1.89, 95%CI 1.11 to 3.20). Additionally, high expression of Ki-67 was identified as a prognosis biomarker for poor PFS of meningioma patients (HR = 1.02, 95%CI 1.00 to 1.04). Although only in single studies, KPNA2, CDK6, Cox-2, MCM7 and PCNA are proposed as additional markers with high expression that are related with poor prognosis of meningioma patients. In conclusion, the results of the meta-analysis demonstrated that PR, cyclin A, TOP2A, p21, p53, VEGF and Ki-67 are either positively or negatively associated with survival of meningioma patients and might be useful biomarkers to assess the prognosis.
Topics: Meningioma; Humans; Biomarkers, Tumor; Prognosis; Meningeal Neoplasms; DNA Topoisomerases, Type II; Ki-67 Antigen; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Immunohistochemistry; Poly-ADP-Ribose Binding Proteins
PubMed: 38758750
DOI: 10.1371/journal.pone.0303337 -
Archives of Gerontology and Geriatrics Oct 2023Cellular senescence (CS) is a permanent arrest of cell growth and exit of the cell cycle. It is an important tumor suppression mechanism and has a key role in wound... (Review)
Review
Cellular senescence (CS) is a permanent arrest of cell growth and exit of the cell cycle. It is an important tumor suppression mechanism and has a key role in wound healing, tissue regeneration, and prevention of tissue fibrosis. Despite the short-term benefits of CS, accumulation of senescent cells has deleterious effects and is associated with several pathological age-related phenotypes. As Heat Shock Proteins (HSP) are associated with cyto-protection, their role in longevity and CS became a research interest. However, an overview of the relationship between HSP and CS in humans still lacks in the literature. To provide an overview of the current state of the literature, this systematic review focused on the role of HSP in the development of CS in humans. PubMed, Web of Science and Embase were systematically screened for studies on the relationship between HSP and CS in humans. A total of 14 articles were eligible for inclusion. The heterogeneity and lack of numerical reporting of outcomes obstructed the conduction of a meta-analysis. The results consistently show that HSP depletion results in increased CS, while overexpression of HSP decreases CS, whether in cancer, fibroblasts, or stem cell lines. This systematic review summarized the literature on the prospective role of HSP in the development of CS in humans.
Topics: Humans; Cellular Senescence; Heat-Shock Proteins; Longevity; Neoplasms
PubMed: 37207540
DOI: 10.1016/j.archger.2023.105057 -
Biology of Sex Differences Jan 2024The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment.
METHODS
A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms.
RESULTS
Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process.
CONCLUSIONS
Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information.
Topics: Humans; Male; Female; Alzheimer Disease; MicroRNAs; Brain
PubMed: 38297404
DOI: 10.1186/s13293-024-00588-1 -
The Journal of Clinical Endocrinology... Oct 2023Tumor-induced osteomalacia (TIO) due to fibroblast growth factor 23 (FGF23) overexpression is becoming recognized in patients with malignancy. The condition may be... (Meta-Analysis)
Meta-Analysis
CONTEXT
Tumor-induced osteomalacia (TIO) due to fibroblast growth factor 23 (FGF23) overexpression is becoming recognized in patients with malignancy. The condition may be underdiagnosed, with a scarce medical literature.
OBJECTIVE
To perform a meta-analysis of case reports to allow a better understanding of malignant TIO and its clinical implications.
METHODS
Full texts were selected according to strict inclusion criteria. All case reports were included where patients had hypophosphatemia, malignant TIO, and FGF23 blood levels. Thirty-two of 275 eligible studies (n = 34 patients) met inclusion criteria. A list of desired data was extracted and graded for methodological quality.
RESULTS
Prostate adenocarcinoma (n = 9) were the most tumors reported. Twenty-five of 34 patients had a metastatic disease and a poor clinical outcome was reported for 15 of 28 patients. The median levels of blood phosphate and C-terminal FGF23 (cFGF23) were 0.40 mmol/L and 788.5 RU/mL, respectively. For most of patients, blood PTH was elevated or within range, and calcitriol levels were inappropriately low or normal. Alkaline phosphatase concentrations were increased for 20 of 22 patients. The cFGF23 values were significantly higher for patients with a poor clinical outcome when compared to other patients (1685 vs 357.5 RU/mL). In case of prostate cancer, cFGF23 levels were significantly lower (429.4 RU/mL) than for other malignancies (1007.5 RU/mL).
CONCLUSION
We report for the first time a detailed description of the clinical and biological characteristics of malignant TIO. In this context, FGF23 blood measurement would be of value for the diagnostic workup, prognostication, and follow-up of patients.
Topics: Humans; Male; Calcitriol; Fibroblast Growth Factors; Hypophosphatemia; Osteomalacia; Paraneoplastic Syndromes; Case Reports as Topic
PubMed: 37235783
DOI: 10.1210/clinem/dgad297 -
Future Oncology (London, England) Jun 2024FAT10, a ubiquitin-like modifier protein, influences apoptosis, DNA damage response and tumor growth, with unclear effects on cancer prognosis. We reviewed... (Review)
Review
FAT10, a ubiquitin-like modifier protein, influences apoptosis, DNA damage response and tumor growth, with unclear effects on cancer prognosis. We reviewed expression's impact on malignancy prognosis through a systematic review and meta-analysis, including studies up to September 2023 from PubMed, EMBASE and Web of Science. From 18 studies involving 2513 patients, overexpression significantly reduced overall and disease-free survival across various tumors, indicating correlations with advanced disease stage, poor differentiation, lymph node metastasis and larger tumor size. 's overexpression suggests a negative prognostic value in cancer, meriting further investigation. CRD42023431287.
PubMed: 38864667
DOI: 10.1080/14796694.2024.2357531 -
Pathology, Research and Practice Aug 2023Management of oral potentially malignant disorders (OPMDs) is still challenging. Despite the diagnostic ascertainment by bioptic examination, this method is poorly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Management of oral potentially malignant disorders (OPMDs) is still challenging. Despite the diagnostic ascertainment by bioptic examination, this method is poorly informative of the prognosis and subsequent malignant transformation. Prognosis is based on histological findings by grading of dysplasia. Immunohistochemical expression of p16 has been investigated in different studies, with controversial results. In this scenario, we systematically revised the current evidence about p16 immunohistochemical expression and the risk of malignization of OPMDs.
MATERIAL AND METHODS
After a proper set of keywords combination, 5 databases were accessed and screened to select eligible studies. The protocol was previously registered on PROSPERO (Protocol ID: CRD42022355931). Data were obtained directly from the primary studies as a measure to determine the relationship between CDKN2A/P16 expression and the malignant transformation of OPMDs. Heterogeneity and publication bias were investigated by different tools, such as Cochran's Q test, Galbraith plot and Egger and Begg Mazumdar's rank tests.
RESULTS
Meta-analysis revealed a twofold increased risk to malignant development (RR = 2.01, 95% CI = 1.36-2.96 - I = 0%). Subgroup analysis did not highlight any relevant heterogeneity. Galbraith plot showed that no individual study could be considered as an important outlier.
CONCLUSION
Pooled analysis showed that p16 assessment may arise adjunct tool to dysplasia grading, leading to an optimized determination of the potential progression to cancer of OPMDs. The p16 overexpression analysis by immunohistochemistry techniques has a multitude of virtues that may facilitate its incorporation in the day-to-day prognostic study of OPMDs.
Topics: Humans; Cyclin-Dependent Kinase Inhibitor p16; Biomarkers, Tumor; Prognosis; Precancerous Conditions; Mouth Neoplasms
PubMed: 37406376
DOI: 10.1016/j.prp.2023.154656 -
Immunity, Inflammation and Disease Jan 2024Glucocorticoids are the most commonly used anti-inflammatory drugs for a variety of diseases, despite the fact that resistance to them is growing in a number of... (Review)
Review
BACKGROUND
Glucocorticoids are the most commonly used anti-inflammatory drugs for a variety of diseases, despite the fact that resistance to them is growing in a number of conditions. There is currently no biomarker that can be used to identify steroid resistance. According to a number of studies, an overexpression of the glucocorticoid receptor beta (GR-β) isoform is associated with steroid-resistant illness. Our goal is to find out whether or not steroid-resistant disorders are associated with an increased level of GR-β expression.
METHODS
We conducted searches in the databases of Web of Science and PubMed until January 17, 2023. This systematic review was done according to the preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Joanna Briggs Institute Appraisal scale was used to assess the quality of the included studies.
RESULTS
After the initial search, we identified 556 papers and finally included 20 studies. Twelve of these studies found an elevated level of GR-β in the steroid resistant group. All five studies on asthma, two out of three on nasal polyps, both studies on ulcerative colitis found an up regulation of GR-β in steroid resistant group as compared to steroid-sensitive groups. GR-β was also shown to be elevated in patients with allergic rhinitis, Crohn's disease and rheumatoid arthritis. In the majority of the investigations, higher levels of GR-β were identified in peripheral blood mononuclear cells through the use of reverse transcription polymerase chain reaction.
CONCLUSION
GR-β was associated with steroid-resistant diseases. It was overexpressed in steroid-resistant diseases and has the potential to be used as a biomarker for disorders involving steroid resistance.
Topics: Humans; Leukocytes, Mononuclear; Receptors, Glucocorticoid; Glucocorticoids; Up-Regulation
PubMed: 38270313
DOI: 10.1002/iid3.1137 -
BMC Oral Health Sep 2023Recently, a systematic review and meta-analysis demonstrated that overexpression of p53 immunoprotein was significantly associated with progression risk of oral... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recently, a systematic review and meta-analysis demonstrated that overexpression of p53 immunoprotein was significantly associated with progression risk of oral potentially malignant disorders (OPMD). However, the results of investigations on TP53 genetic typing in OPMD were inconsistent and inconclusive.
METHODS
A systematic evaluation was conducted to identify all eligible case-control studies on the association of TP53 codon 72 polymorphism with both onset and progression of OPMD.
RESULTS
A total of 768 OPMD patients and 1173 healthy individuals were identified from 12 eligible case-control studies on TP53 codon 72 polymorphism OPMD onset. In overall and subgroup analyses, no significantly risk of OPMD onset was observed in the cases for genetic models including allele C vs. G, homozygote CC vs. GG, heterozygote GC vs. GG, dominant GC + CC vs. GG, and recessive CC vs. GG + GC (all P-value of association test > 0.05). Further, a total of 465 OPMD patients and 775 oral squamous cell carcinoma (OSCC) ones were identified from 8 eligible case-control studies on this polymorphism in OPMD progression to OSCC. The analyses revealed that there was also no significantly risk of OPMD progression in the cases for the genetic models (all P-value of association test > 0.05).
CONCLUSION
Our data of a pooled-analysis indicates that TP53 codon 72 polymorphism may not act as genetic factor for the risk of OPMD onset and progression. Combined with the conclusion by a systematic review and meta-analysis, we put forward a new opinion that TP53 genetic typing cloud not influence p53 protein expression in OPMD.
Topics: Humans; Tumor Suppressor Protein p53; Mouth Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Codon
PubMed: 37697274
DOI: 10.1186/s12903-023-03316-0